Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST
Abstract
:1. Introduction
2. Results
2.1. Generation and Characterization of Primary Cell Lines from Patients with Diagnosis of KIT/PDGFRA WT GIST
2.2. wtGISTc Are Resistant to Imatinib and Moderately Sensitive to Sunitinib
2.3. Generation and Characterization of CIK Lymphocytes from GIST Patients
2.4. CIK Are Capable of Direct and Indirect Cancer Cell Killing and Immunomodulation in wtGISTc Resistant to TKI
2.5. Antitumor and Immunomodulatory Activity of IFNα and IFNγ in wtGISTc
3. Discussion
4. Materials and Methods
4.1. Experimental Platform and Generation of Wild-Type Primary GIST Cell Lines
4.2. CIK Cells Culture and Ex Vivo Expansion
4.3. Flow Cytometry
4.4. mRNA Analysis
4.5. DNA Sequencing Analysis and Gene Mutation Profile
4.6. In Vitro Drug Sensitivity and Cancer Cell Killing Assays
4.7. In Vitro Soluble Factors Production
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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wtGISTc | Gene Name | Variant Type | Single Nucleotide Variant ID | VAF (%) | Fold Change |
---|---|---|---|---|---|
S012 | SPEN | inframe_deletion | chr1_16260673_CCTCACTGGTCTGGTGAGCGCA_C | 27 | |
LATS2 | missense_variant | chr13_21562627_G_A | 36 | ||
JAK2 | amplification | chr9 | 1.946 | ||
PTEN | amplification | chr10 | 1.445 | ||
S061 | / | / | / | / | |
S075 | / | / | / | / | |
S108 | NOTCH1 | missense variant:splice region variant | chr9_139401170_G_A | 51 | |
S125 | / | / | / | / | |
S148 | ARID1B | missense_variant | chr6_157100551_G_C | 47 | |
PRKDC | missense_variant | chr8_48805728_C_G | 24 | ||
S173 | MYCN | missense_variant | chr2_16082319_C_T | 20 | |
GNAS | missense_variant | chr20_57474036_G_T | 19 | ||
S188 | PGR | missense_variant | chr11_100998322_C_G | 31 | |
S220 | HIST3H3 | missense_variant | chr1_228612992_G_A | 16 | |
LRP1B | missense_variant | chr2_141201961_G_T | 19 | ||
CUL3 | missense_variant | chr2_225379486_G_A | 20 | ||
PRKDC | missense_variant | chr8_48866988_T_G | 58 | ||
MALT1 | missense_variant | chr18_56363602_A_G | 16 | ||
NF2 | stop_gained | chr22_30038226_C_A | 50 | ||
FGFR1 | amplification | chr8 | 1.533 | ||
MYC | amplification | chr8 | 1.637 | ||
S243 | IRS1 | stop_gained | chr2_227661875_G_T | 9 | |
PDGFRB | inframe_deletion | chr5_149495390_AGCTCTG_A | 7 | ||
NOTCH4 | missense_variant | chr6_32189007_G_A | 7 | ||
S288 | FGF2 | missense_variant | chr4_123813429_C_T | 51 | |
FAT1 | missense_variant | chr4_187628598_T_C | 46 |
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Fiorino, E.; Merlini, A.; D’Ambrosio, L.; Cerviere, I.; Berrino, E.; Marchiò, C.; Giraudo, L.; Basiricò, M.; Massa, A.; Donini, C.; et al. Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST. Int. J. Mol. Sci. 2022, 23, 10368. https://doi.org/10.3390/ijms231810368
Fiorino E, Merlini A, D’Ambrosio L, Cerviere I, Berrino E, Marchiò C, Giraudo L, Basiricò M, Massa A, Donini C, et al. Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST. International Journal of Molecular Sciences. 2022; 23(18):10368. https://doi.org/10.3390/ijms231810368
Chicago/Turabian StyleFiorino, Erika, Alessandra Merlini, Lorenzo D’Ambrosio, Ilaria Cerviere, Enrico Berrino, Caterina Marchiò, Lidia Giraudo, Marco Basiricò, Annamaria Massa, Chiara Donini, and et al. 2022. "Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST" International Journal of Molecular Sciences 23, no. 18: 10368. https://doi.org/10.3390/ijms231810368